Disease relevance of GSR

• The erythrocyte glutathione-reducing system, represented by G6PDH and glutathione reductase, showed only slight differences among the four groups of children; the supposition that kwashiorkor occurs predominantly in children with aberrant G6PDH could not be substantiated [1].
• The exposure to CBD caused in glioma cells an early production of ROS, depletion of intracellular glutathione and increase activity of glutathione reductase and glutathione peroxidase enzymes [2].
• Trypanosoma and Leishmania, pathogens responsible for diseases such as African sleeping sickness, Chagas' heart disease, or Oriental sore, are two of the very few genera that do not use the ubiquitous glutathione/glutathione reductase system to keep a stable cellular redox balance [3].
• Odds ratio for erythrocytic GR, SOD, CAT and plasma thiol showed significantly higher risk of oral cancer development in WHT [4].
• METHODS: In a population of sarcoidosis (n = 88) patients, G6PD, GR and GR activity after incubation with chromate (GR-Cr) were measured in erythrocytes [5].

Psychiatry related information on GSR

• In conclusion our results suggest that increased activities of erythrocyte GPx and decreased erythrocyte GR activities might be due to lesser physical activity of children with CP [6].
• No significant differences were observed in erythrocyte glutathione peroxidase, glutathione reductase and catalase activities, between the Rett syndrome patients and the control group [7].
• The activities of glutathione peroxidase and glutathione reductase were unaffected in Alzheimer's disease [8].
• Marijuana has been found to interfere with both paired-associate learning and phasic GSR activity [9].
• The purpose of this study was to compare the effects of Benson's relaxation technique (BRT) with Benson's technique augmented with GSR biofeedback (i.e., biofeedback-aided relaxation, BAR) on the psychological stress symptoms of well college students [10].

High impact information on GSR

• An example of two related enzymes that catalyse similar reactions but possess different active sites is provided by comparing the structure of Escherichia coli thioredoxin reductase with glutathione reductase [11].
• Human glutathione reductase serves as a reference molecule for FAD-dependent disulphide reductases and between its primary structure and that of MerA from Tn501 (Pseudomonas), Tn21 (Shigella), p1258 (Staphylococcus) and Bacillus, 25-30% of the residues have been conserved [12].
• Directed mutagenesis and molecular modelling have been used to identify a set of amino-acid side chains in glutathione reductase that confer specificity for the coenzyme NADP+ [13].
• The three-dimensional structure of the dimeric flavoenzyme glutathione reductase from human erythrocytes has been elucidated by an X-ray diffraction analysis at 0.3 nm resolution [14].
• It contains a glutathione reductase-like flavin-binding subunit and a diheme cytochrome subunit [15].

Chemical compound and disease context of GSR

• Glutathione reductase and nitroblue tetrazolium reduction deficiencies in neutrophils of patients with primary idiopathic myelofibrosis [16].
• Furthermore, plasma and erythrocyte MDA levels, and the SOD and GR activities in erythrocytes significantly increased in hepatitis C patients compared to the controls [17].
• The level of thiobarbituric acid-reactive products and the specific activities of catalase and glutathione reductase were significantly higher in muscles from patients with major forms of muscular dystrophies over those of control subjects [18].
• CONCLUSION: The levels of Zn, Se, Cu, and oxidative stress (MDA), as well as related anti-oxidative enzymes (GR and GPX) in blood have important impact on the viral factors in chronic hepatitis C [17].
• Under standard culture conditions (100 microM cystine, 100 microM tyrosine), the levels of GSH and the activities of glutathione reductase (GR) and GPO were found to be directly related to the pigmentation of melanoma cells [19].

Biological context of GSR

• Sequence-tagged site (STS) markers were generated from subclones of 2 GSR YACs and used to identify P1 and cosmid clones [20].
• GSR phenotypes were not related to the haemoglobin types [21].
• We present allele frequencies in Japanese and Caucasian cases and controls for D8S137, D8S131, D8S87, D8S278, D8S259, D8S283, fibroblast growth factor receptor 1, ankyrin 1, D8S339, and two polymorphisms in glutathione reductase (GSR), covering approximately 16.5 cM in total [22].
• Histological differences showing much higher cell damage in females were studied in conjunction with lipid peroxidation and activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase [23].
• These findings, together with the results of kinetic experiments on the release of GSH from SMG and cysteine from SMC, suggested that while both conjugates inhibit GR by carbamoylation of an active-site thiol(s), SMG exhibits a greater affinity for the active site than SMC [24].

Anatomical context of GSR

• Catalase, GPx and GR values were significantly different in the three permanent cell lines [25].
• Catalase and glutathione reductase protection of human alveolar macrophages during oxidant exposure in vitro [26].
• Electron spin resonance spin trapping measurements using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent provided evidence that the incubation of Cr(VI) with the Jurkat cells in the presence of glutathione reductase generated .OH radicals [27].
• Among the enzymic antioxidants, the activities of superoxide dismutase, glutathione peroxidase, and glutathione reductase were higher in the epidermis compared to the dermis by 126, 61 and 215%, respectively [28].
• The up-regulation of three genes in these systems, thioredoxin (P < 0.005), thioredoxin reductase 1 (P < 0.001) and glutathione reductase (P < 0.001) was verified with real-time RT-PCR, using human macrophages from 10 healthy donors [29].

Associations of GSR with chemical compounds

• GSR and GPX activity, which was lower in FUra-adapted than in parental cells only at post-confluence, could be considered as markers of differentiated cells [30].
• Neither did treatment with 1,25(OH)2D3 affect the levels of glutathione reductase or glutathione S-transferase as assayed in cell extracts [31].
• Glutathione reductase is the principal enzyme involved in the regeneration of GSH from GSSG [32].
• Simultaneous induction of sod, glutathione reductase, GSH, and ascorbate in liver and kidney correlates with survival during aging [33].
• Glutathione reductase and NADPH enhanced Cr(V) generation [27].

Physical interactions of GSR

• GSHPx coupled to reduced nicotine adenine diphosphate (NADPH) regenerating systems via glutathione reductase is virtually able to guarantee an effective protection of biological structures against oxidative attack (22) [34].
• The topologies and spatial arrangements of these two domains are remarkably similar to the FAD- and NADPH-binding domains of glutathione reductase [35].

Enzymatic interactions of GSR

• Reduction of the antioxidant lipoic acid has been proposed to be catalyzed in vivo by lipoamide dehydrogenase (LipDH) or glutathione reductase (GR) [36].
• The mode of binding of NADPH and oxidized glutathione to the flavoenzyme glutathione reductase has been determined by x-ray crystallography [37].
• The NADPH used by glutathione reductase for the reduction of oxidized glutathione (GSSG) to GSH is also used by aldose reductase for the reduction of glucose to sorbitol through the polyol pathway [38].

Regulatory relationships of GSR

• To investigate the relative importance of catalase and the glutathione redox cycle, the experiments were conducted in cells pretreated with amino-triazole (ATZ) to inactivate catalase or with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to inactivate glutathione reductase [26].
• The use of DTNB in the initial staining step inhibits enzymes other than glutathione reductase that could be stained with the dichlorophenolindophenol/nitroblue tetrazolium counterstain [39].
• Glutathione reductase (GR) induction (185% of control 2 d after inoculation) was insufficient to overcome the decreased antioxidant potential of glutathione [40].
• The reduction of ubiquinone by lipoamide dehydrogenase and glutathione reductase is potently stimulated by zinc and the highest rate of reduction is achieved at acidic pH and the rates are equal with either NADPH or NADH as co-factors [41].
• Similarly, reduction of SP-A and SP-B mRNA levels following accumulation of GSSG induced by glutathione reductase inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), supports the hypothesis that surfactant protein synthesis is reduced in response to oxidation of pulmonary epithelial glutathione [42].

Other interactions of GSR

• We show that three of the markers examined--D8S339 and both polymorphisms in the GSR locus--show strong statistically significant evidence of disequilibrium with WRN in the Japanese population but not in the Caucasian population [22].
• No differences in levels of glutathione, catalase, superoxide dismutase, glutathione S-transferase, or glutathione reductase were noted in MCF-GPX-6 cells compared to MCF-7WT cells [43].
• The enzyme activities of the three permanent cell lines were either higher (SOD, catalase, GR) or lower (GST, GPx) than in the primary cell cultures [25].
• In order to estimate the ability of the cultures to produce NADPH (an important component of cellular redox status and a cofactor for GR), we determined glucose-6-phosphate dehydrogenase activity and mRNA abundance [44].
• One hour photolysis of the human lens WS fraction under anaerobic conditions yielded an almost complete inactivation of GR, but only an 18% loss of G3PD activity [45].

Analytical, diagnostic and therapeutic context of GSR

• The use of glutathione reductase inhibitors in chemotherapy is the raison d'être for this study [46].
• In all three patient groups, GR activity was higher than in the control group [47].
• In this study, erythrocyte catalase, glutathione peroxidase and glutathione reductase enzyme activities were determined in patients undergoing cardiopulmonary bypass [48].
• 3. The paper completes the sequence analysis of glutathione reductase so that the enzyme is now known in atomic detail [49].
• Tissue distributions of GR were examined by Northern and Western blotting with a rabbit antibody to purified GR [50].

References